Pharmacokinetics of nicorandil in dogs with mild mitral regurgitation.

The aim of this study was to examine the pharmacokinetics of nicorandil, a hybrid of an adenosine triphosphate-sensitive potassium channel opener and a nitrate, and to estimate its clinical doses in dogs with mild mitral valve regurgitation (MR). Nicorandil (0.1, 0.3, and 1.0 mg/kg) was administered orally to normal dogs and those with experimentally-induced MR, and its plasma concentrations were analyzed using high-performance liquid chromatography. Plasma concentrations increased dose-dependently after the administration of nicorandil, and were not different between normal dogs and those with MR. Similar to the effective plasma values obtained in cardiac disease in humans, the findings of this pharmacokinetic study may indicate that a dose of 0.3-1.0 mg/kg has the same effectiveness in dogs with cardiac dysfunction.

Correlation between heart rate variability and haemodynamic fluctuation during induction of general anaesthesia: comparison between linear and non-linear analysis.

The objective of this study was to compare linear and non-linear analysis of heart rate variability (HRV) in terms of correlation with haemodynamic fluctuation during induction of general anaesthesia. Pre-operatively, HRV was estimated by the MemCalc method in 114 patients scheduled for general anaesthesia. After anaesthesia was induced with propofol, fentanyl and vecuronium bromide, tracheal intubation was performed. Haemodynamic fluctuations during induction of anaesthesia were recorded and the correlation between pre-operative HRV and haemodynamic fluctuation was examined using logistic regression analysis. As an index of non-linear analysis of HRV, ultra short-term entropy (UsEn) correlated better with blood pressure fluctuation than did the ratio of the power of low frequency component of HRV to that of high frequency component (LF/HF). In contrast, although LF/HF significantly correlated with heart rate increase caused by tracheal intubation, the correlation between UsEn and heart rate fluctuation was not significant.

A semi-immobilization of a partial auricle induces hypertrophy and ultrastructural alteration of cardiomyocytes.

Semi-immobilization of a partial area of the ventral edge, lateral epicardium of the left auricle (ventrolateral of left auricle), by using quick adhesion glue induces moderate hypertrophy of myocytes with an average increase of 34% in cross-sectional area. Intercellular connective tissues increased, and cellular sizes varied markedly. The ultrastructure of immobilized (semi-immobilized) myocytes commonly exhibited degenerating features in myofibrils, various cytoplasmic organelles including mitochondrial cristae and sarcoplasmic reticulum (SR) were disrupted, and T-tubules disappeared. Z-line streaming and widening (hypertrophic Z-line, rod bodies) and increase of metabolic particle deposition are typical phenomena in addition to intercalated disc (Id) disorganization. The results suggest that semi-immobilization of the auricle induces hypertrophy of myocytes in association with degeneration and disruption of myofibrils and other cytoplasmic organelles, and an increase of intercellular connective tissues, rather than increase of myofibril mass. This is the first study to immobilize only a part of the heart rather than the whole animal. Our results using artificial immobilization of cardiac myocytes were extremely significant since the structural alterations obtained were similar to that observed in cardiomyopathies. This suggests that myocytes progressing to heart failure are also subjected to inhibition of movement. Therefore, this experiment may prove very useful as a model for studying the functional effect of heart failure observed in cardiomyopathy.

Aberrant branch of the bronchoesophageal artery resembling patent ductus arteriosus in a dog.

An anomalous shunt between the bronchoesophageal artery and pulmonary artery was diagnosed in a 1-year- old, 3.5 kg female Miniature Dachshund by selective contrast angiography. A cardiac murmur had been observed in the dog during examination at another hospital. The machinery murmur was auscultated at the left side of the base of the heart. Although thoracic radiography revealed mild cardiomegaly, the characteristic findings of patent ductus arteriosus (PDA), including as aortic arch enlargement and pulmonary artery enlargement were not observed. Echocardiography demonstrated shunting of blood flow presumably from the arterial duct at the pulmonary artery carina. Based on the above findings the case was diagnosed as PDA. Angiocardiography was performed to confirm the diagnosis in preparation for surgical treatment, but later we confirmed that the shunt vessel was not PDA, but apparently a branch of the bronchoesophageal artery. The shunt vessel was branching in a complicated manner and shunted to the pulmonary artery.

Hypertrophic cardiomyopathy in two kittens.

Two 2-month-old kittens presented with a loud cardiac murmur. One cat showed severe signs of heart failure such as respiratory effort and exercise intolerance. Echocardiography revealed left ventricular concentric hypertrophy and severe left ventricular outflow obstruction. They died at 5 and 12 months of age, respectively. Necropsy and histopathology confirmed hypertrophic cardiomyopathy.

Medical dissolution of struvite nephrolithiasis using amino acid preparation in dogs.

A new chemolytic therapy with amino acid preparation was tried for use on struvite renal stones in two dogs, which were admitted to Azabu University Veterinary Teaching Hospital. No other special diet, for the purpose of dissolving the stones, was fed during the treatment. Dissolution of the stones began at week 1, and no stone was detected on radiography at week 4 in both cases. The amino acid preparation thereafter has been administered every 2-3 days to prevent formation of the stones. After 6 months from treatment, complete dissolution was confirmed, and no relapse has been observed. Therefore, it is concluded that chemolytic therapy with amino acid preparation might be useful for the treatment of nephrolithiasis with struvite renal stones in dogs.

A clinical study on velocity patterns of pulmonary venous flow in canine heartworm disease.

In this study, we evaluated methods of determining the velocity patterns of pulmonary venous flow (PVF) in dogs and then investigated the relationship of the patterns to cardiac functions in heartworm disease (HD) by transthoracic echocardiography (TTE). The results revealed that there was a good correlation between PVF patterns determined by transesophageal echocardiography (TEE) and TTE in animals lying on their left sides. The measurement of S and D wave velocities (PVS and PVD) by TTE was shown to allow clinical determination of the velocity patterns of PVF in dogs. The HD groups showed significant increases in PVS and PVD, and S and D wave time-velocity integrals (S-TVI and D-TVI) of the right cranial lobe PVF, when compared with the normal group, as determined by TTE (P<0.05). In contrast, the HD groups produced significant decreases in PVD and D-TVI of the right caudal lobe PVF compared with the normal group (P<0.05), and a significant increase in the ratio of S-TVI to (S-TVI + D-TVI) (P<0.05). It is, therefore, suggested that measurement of the velocity patterns of the right cranial and caudal lobe PVF could be one method of assessing the stages of obstructive lesions in the pulmonary artery.

Diurnal variations of blood pressure in dogs.

Using the telemetry system, we measured the blood pressure (BP) invasively in seven adult mongrels while unanesthetized and unbound. Post-operative BP after implanting the telemetry BP transmitter showed temporarily high values due to the invasive nature of the surgery. It was, however, observed that BP gradually decreased thereafter, and showed settled trends from the eighth day post-operatively. When we took the average of the systolic, mean and diastolic BP at hourly intervals for each of the dogs once their BP had settled, a twin peak diurnal variation (at 8:00 and 19:00) was observed. Moreover, significantly high values (p < 0.05) were identified in active state compared with when sleeping or at rest. The 24 hr BP measured by the telemetry system in seven normal dogs resulted in the following values: systolic 123.4 +/- 7.9 mmHg, mean 91.1 +/- 5.6 mmHg, and diastolic 74.5 +/- 4.9 mmHg.

The circadian variation of urinary N-acetyl-beta-D-glucosaminidase and gamma-glutamyl transpeptidase in clinically healthy cats.

The circadian variation of urinary N-acetyl-beta-D-glucosaminidase (NAG, EC 3.2.1.30) and gamma-glutamyl transpeptidase (gamma-GTP, EC 2.3.2.2) was evaluated in cats. Urine and blood were collected at 4-hr intervals from adult cats (3 males, 9 females) weighing between 2.6 and 5.0 kg. There was no circadian variation in the urine volume, creatinine clearance, creatinine excretion, NAG excretion or gamma-GTP excretion. The average NAG and gamma-GTP indices in the 4-hr urine were similar to those for the 24-hr urine. However, the variance for the 4-hr urine samples was higher than that of 24-hr urine. In conclusion, although 4-hr urine samples can be used to estimate 24-hr urinary enzyme excretion, short-term spot urine samples may cause increased variation in the enzyme index.

Non-invasive blood pressure measurements in cats: clinical significance of hypertension associated with chronic renal failure.

The systolic, mean and diastolic pressures as well as the heart rate were measured using the oscillometric method, on a total of 104 cats (60 cats in the normal group, and 44 in the renal disease group) which were brought into Azabu University Animal Hospital. The blood pressure in the normal group was systolic: 115.4 +/- 10.1 mmHg, mean: 96.2 +/- 12.2 mmHg, and diastolic: 73.7 +/- 10.7 mmHg. Although no difference in heart rate, the renal disease group showed significantly (p < 0.05) higher values for systolic, mean, and diastolic pressure when compared with the normal group. Moreover, when plasma renin activity, angiotensin I and II, and aldosterone concentrations were measured in other cats (11 normal and seven with chronic renal failure), all cats with chronic renal failure showed significantly (p < 0.05) higher values than the normal group. It is, therefore, indicated that hypertension due to stimulating renin-angiotensin-aldosterone system may have manifested in cats with renal dysfunction.

A clinical evaluation of blood pressure through non-invasive measurement using the oscillometric procedure in conscious dogs.

The oscillometric procedure was used to measure the heart rate as well as the systolic, mean, and diastolic blood pressures of 152 dogs (102 in the control group, 13 in the group with renal disease, 37 in the group with heart disease) who were brought to Azabu University of Veterinary Teaching Hospital. It was demonstrated that the blood pressure and heart rate of the control group lowered and tended to become stable as the number of measurements increased. No appreciable difference was identified in the measurements of either blood pressure or heart rate in the forelimbs and tail head. With regard to gender, males showed a significantly higher value than females (p < 0.05). No interaction was identified between age and blood pressure. No difference was identified in the heart rate in all groups. In an investigation of blood pressure in all groups, the renal disease group showed significantly higher values (p < 0.05) than either the control or the heart disease group in all values of systolic, mean and diastolic pressures. These results indicated that dogs with renal disease can manifest hypertension.

The variation in excretory urinary glycyl-prolyl dipeptidyl aminopeptidase in dogs.

We studied the excretory variation of urinary glycyl-prolyl dipeptidyl aminopeptidase (GP-DAP, EC 3.4.14.5) in dogs. Adult domestic mongrel dogs (seven males and nine females, 7.5 to 13 kg bodyweight) which were considered to be healthy by laboratory tests were used. Urine and blood samples were obtained every four hours. Urine volume was measured for each sample and urine GP-DAP activity, and creatinine levels were determined. Creatinine clearance, creatinine excretion, GP-DAP activity and GP-DAP index (GP-DAP/Cr ratio) did not show any significant variation between the time periods. However, urine volume and urinary GP-DAP excretion significantly increased from 8:00 am to 12:00 pm. The GP-DAP index in spot urine samples showed low correlation with 24 hour GP-DAP excretion. In addition, a sex difference was observed in GP-DAP excretion. In conclusion, urinary GP-DAP excretion showed a circadian variation and sex difference. Therefore, GP-DAP in spot urine is not of use for the detection of renal disorders, and the 24-hour excretion value of GP-DAP should be determined.

Relationship between degree of mitral protrusion assessed by use of B-mode echocardiography and degree of mitral regurgitation using an experimental model in dogs.

We studied the relationship between the degree of mitral protrusion and degree of mitral regurgitation in an experimental model in which the degree of mitral protrusion could be adjusted. The model was developed by dissecting the dorsal papillary muscle through a left atriotomy in 5 dogs and re-attaching the papillary muscle to the original site using a single mattress suture threading through the epicardium under cardiopulmonary bypass. By manipulating the suture from a position outside the epicardium, the degree of mitral protrusion could be adjusted. The long-axis view of the mitral valve was imaged by B-mode echocardiography with the transducer placed directly over the surface of the right ventricular outflow tract. The height (H) from the coaptation point or tip of the protruded cusp in relation to the mitral annular plane was measured as an index of mitral protrusion. Mitral regurgitation as a result of the mitral protrusion decreased the left ventricular systolic pressure, and increased the heart rate, mean left atrial pressure (LAPm), and ratio of left ventricular end-diastolic dimension to body weight (LVEDD/BW). H was negatively correlated to LAPm and LVEDD/BW (r = -0.723 and -0.697, respectively). Our results indicated that H expresses not only the degree of mitral protrusion but also the degree of mitral regurgitation, and were in agreement with the previous findings obtained on dogs with spontaneous mitral regurgitation.

Idiopathic renal hematuria in a dog; the usefulness of a method of partial occlusion of the renal artery.

Exploratory laparotomy was performed on a dog suspected of having idiopathic renal hematuria. Two catheters were inserted into the bilateral ureters, and hematuria from the left kidney was confirmed. The blood flow was occluded in the ventral and dorsal rami of the left renal artery in order to localize the site of hemorrhage. As hematuria disappeared when the dorsal ramus was occluded, the site of renal hematuria was localized to the area dominated by the dorsal ramus of the renal artery. As a result of ligating the dorsal ramus of the left renal artery in this dog, renal hematuria subsided, and the dog has shown a favorable course, to date, one year after surgery.

Renal transplantation in cats with chronic renal failure.

Renal transplantation was performed on 6 cats with chronic renal failure. Clinical signs and the blood chemistry findings (BUN, Cr, IP) improved one week after renal transplantation. Renal anemia also improved 3-4 weeks after surgery. Two cases had the same complications, hydronephrosis and hydroureter within 1 or 2 weeks of surgery, evidenced by marked elevations of BUN and Cr, suggesting that ureteral obstruction at the site of ureterocystostomy is the main complication of renal transplantation in cats. As a new resolution for this problem, we transplanted the ureter with the intact ureteral opening of the bladder from the donor in the remaining 4 cats. Ureteral obstruction was not observed in them, thus the procedure was considered to be useful for avoiding this complication. Two cats died of pneumonia and other complications within 3 months. There were no acute rejections or side effects from the immunosuppressant during the observation period in the remaining four cats.

Mitral valve protrusion assessed by use of B-mode echocardiography in dogs with mitral regurgitation.

OBJECTIVE: To examine our hypothesis that changes of the mitral valve in dogs with mitral regurgitation lead to various degrees of protrusion of the cusp in individual dogs in systole. DESIGN: Assessing the mitral protrusion, using B-mode echocardiography in dogs with mitral regurgitation. ANIMALS: 33 dogs with chronic mitral regurgitation and 40 clinically normal dogs. PROCEDURE: The mitral valve was imaged in the right parasternal left ventricular long-axis view, and we measured the height (H) from the coaptation point or tip of the protruded cusp to the mitral annular plane. When the tip of the protruded cusp was located beyond the mitral annular plane extending into the left atrium, H was expressed as negative values. RESULTS: The H in clinically normal dogs was 3.7 +/- 0.8 mm. In dogs with mitral regurgitation, the mitral cusp protruded toward the left atrium to various degrees, and H was -0.7 +/- 1.9 mm (range, 2.9 to -5.0 mm). The 2 dogs in the latter group with the lowest H (-5.0 and -4.5 mm, respectively) presented typical mitral flail on B-mode images. The indices of left atrial and ventricular dimension (left atrial dimension/aortic dimension and left ventricular end-diastolic dimension/body weight, respectively) were significantly higher than those in the clinically normal dogs and were negatively correlated with H. CONCLUSION: The mitral valve in individual dogs with mitral regurgitation has different degrees of protrusion. The degree of protrusion might be related to the hemo-dynamic condition in mitral regurgitation.

Intrahepatic portal-venous changes in dogs with dirofilariasis: scanning electron microscopy of resin casts of vasculature.

Intra hepatic portal-venous changes in dogs with dirofilariasis, in which characteristic cavernous transformation has been histologically observed, were studied by scanning electron microscopy (SEM) of resin casts of vasculature. Changes in the central and sublobular veins were the most significant. The venous channels were extremely dilated, thin-walled and showed cavernous structure. SEM observation showed multi-saccular formation with beads-like, helical and extremely dilated configuration. The conducting venules, i.e. terminal tributaries of the portal vein, showed a rapid taper just before the point of merging into sinusoids. Neither vascular proliferation nor collateral circulation around the portal channels could be detected in the present resin cast study.

Proximal paraconal interventricular myocardial bridge in dog: ultrastructural characterization.

The ultrastructure of the dog myocardial bridges (MB), named here the proximal paraconal interventricular-myocardial bridge (PPI-MB), was examined to determine if its structure is identical to that of ordinary cardiac muscle. This study is preparatory to the establishment of PPI-MB as a physical and physiological model system to examine the influence of MB on coronary flow in cardiac function. Five of 46 dog hearts examined possessed PPI-MB, the occurrence of which was independent of sex, age and breed. The dog PPI-MB was localized in a limited area in the proximal third of the paraconal interventricular groove. PPI-MB myocytes and myofibrils were arranged quite straight and smooth, with minimum branching. PPI-MB myocytes formed side-by-side cell junctions through the mediation of mitochondria. Connective tissue elements were involved in terminal cell adhesion to form the myomyous junction beside the intercalated disc. The excitation conductive system of sarcoplasmic reticulum-T tubule often showed a triad. Numerous nerve axons or nerve ending-like structures appeared. Many structural views deviated somewhat from common cardiac muscle structure. This paper represents the first detailed description of PPI-MB muscle.

Circadian variation of urinary enzymes in the dog.

Circadian variations of N-acetyl-beta-D-glucosamidase (NAG, EC 3.2.1.30) and gamma-glutamyl transpeptidase (gamma-GTP, EC 2.3.2.2) were examined in dogs. Urine and blood were collected at 4-hr intervals from adult mongrel dogs (11 males, 11 females) weighing between 7 and 13 kg. The collected urine and blood were used to measure creatinine, NAG and gamma-GTP. The amount of urine was significantly higher (p < 0.05) during the period from 12:00 to 16:00. Creatinine clearance did not show any characteristic variations and creatinine excretion was significantly higher (p < 0.05) during the period from 8:00 to 16:00. No characteristic variations were observed in the amounts excreted, activity, or NAG and gamma-GTP creatinine index. There were high correlations between creatinine excretion and creatinine clearance (r = 0.693), gamma-GTP excretion and gamma-GTP creatinine index (r = 0.724), NAG excretion and NAG creatinine index (r = 0.878), and between the NAG and gamma-GTP creatinine index of each 4-hr specimen and the NAG and gamma-GTP excretion of the 24-hr specimens. These results suggest the diagnostic usefulness measuring enzyme activity in non-periodically collected urine.